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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (in combination with an aminoglycoside, when indicated)
## Adult Dosing
Standard dose: 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 6 hours.
* For severe infections or those caused by *Pseudomonas aeruginosa*, doses of 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) every 6 or 8 hours may be used.
* Maximum daily dose for non-renal impairment is typically 18 grams (16 grams piperacillin/2 grams tazobactam) per day.
## Pediatric Dosing
Dosing in pediatric patients is typically based on piperacillin content and varies by indication and age/weight. Consult specific institutional protocols or pediatric infectious disease guidelines for precise dosing. General guidelines are as follows:
* **Patients 2 months of age and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours.
* **Complicated skin and skin structure infections:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose every 6 hours.
* **Hospital-acquired pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours.
* **Maximum dose per administration:** Generally does not exceed 4.5 grams per dose.
## Dose Adjustments
**Renal Impairment (CrCl mL/min):**
* **CrCl 20-80 mL/min:** 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours or 4.5 grams (4g piperacillin/0.5g tazobactam) every 8 hours.
* **CrCl < 20 mL/min:** 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours.
* **Hemodialysis:** 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours, with an additional 0.75 gram dose after each dialysis session.
Dosing requires careful consideration of the severity of infection and patient-specific factors.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of severe allergic reaction to other beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, pruritus, headache, insomnia, fever.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (particularly with high doses or renal impairment), neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function (AST, ALT, bilirubin)
* Complete blood count (especially for prolonged therapy or suspected hematologic effects)
* Signs and symptoms of infection
* Electrolytes (especially if given with other drugs affecting electrolytes)
* INR if patient is on warfarin
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often used for empiric therapy of serious infections, including those involving Gram-negatives and anaerobes.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* The beta-lactamase inhibitor tazobactam protects piperacillin from degradation by many beta-lactamases, extending its spectrum of activity.
* Due to the potential for seizures, caution is advised in patients with renal impairment or a history of seizures, and the maximum recommended dose should not be exceeded.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols before administering any medication.*
